1. Adrenal Dysfunction following Cardiac Surgery
JM Co, MD, FPCP, FPSEM
Endocrinology, diabetes and metabolism
UERMMMCI
St luke’s medical center QC
Cardinal santos medical center
May 24, 2012

2. Should I be concerned re adrenal dysfunction?
Hypotension post-cardiac surgery? Probably cardiac.
Why is my patient still hypotensive several days after cardiac surgery?
Am I missing something?!
I’m just here for the sugars!
Does he have adrenal dysfunction?

3. Why? Is this condition a common occurrence?
Consider adrenal dysfunction in your post-cardiac surgery patient whom you have difficulty weaning off vasopressors.
Why? Is this condition a common occurrence?

4. Incidence in surgical ICU
Incidence of adrenal insufficiency among surgical ICU patients > 55 years of age with postoperative hypotension requiring vasopressors was as high as
32.7%
Rivers EP, Gaspari M, Saad GA et al. Chest 2001; 119:

5. 120 elective CABG patients
93 had relative adrenal insufficiency (77.5%)
Of the 78 patients who received etomidate, 69 had developed relative adrenal insufficiency (88%)
Of the 42 patients who did not receive etomidate, 24 developed relative Adrenal insufficiency (57.1%)
Iribarren et al. Journal of Cardiothoracic Surgery 2010, 5:26

6. Diagnostic criteria still needs work
ACTH-stimulation tests in CABG patients
38.5% of the clinically euadrenal and maximally stressed surgical patients with an uneventful clinical course showed an inadequate rise of cortisol levels after the 250 ug ACTH-stimulation, when using the 9 ug/dL criterion.
J Clin Endocrinol Metab 90: 4579–4586, 2005

7. The adrenal gland Mineralocorticoids (eg Aldosterone) Glucocorticoids
(eg Cortisol)
Androgens
Catecholamines
(eg Epinephrine)

8. Cortisol 90% bound; 10% free Circulating half-life 70-120 mins
Not stored in the adrenal gland
Binds to intracellular glucocorticoid receptors
Affect the transcription of thousands of genes in every cell of the body.
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

9. Cortisol affects the transcription of thousands of genes in every cell of the body.
Effects
Increases glucose
Activation of lipolysis
Increases sensitivity to vasopressor agents such as catecholamines and angiotensin II
Anti-inflammatory actions
Reduction in the number and function of various immune cells at sites of inflammation
Decreases the production of cytokines, chemokines, and eicosanoids
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

10. Adrenal response to stress
With severe infection, trauma, burns, illness, or surgery, there is an increase in cortisol production by as much as a factor of six that is roughly proportional to the severity of the illness.
Diurnal variation in cortisol secretion is also lost.
These effects are due to increased production of CRH and ACTH and a reduction in negative feedback from cortisol.
Cooper M, Stewart P. N Engl J Med ;8

11. Adrenal response to surgery
Surgery is one of the most potent activators of the hypothalamic-pituitary-adrenal axis
Maximum cortisol levels are reached in the early postoperative period, especially following anaesthesia reversal and endotracheal extubation
In CABG
Peak cortisol levels achieved 30 minutes after extubation
Cortisol levels have high normal values about hours after surgical procedure
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

12. Why would the adrenal fail?
Strong inflammatory signals, such as cytokines (TNF-α) or other peptides, known as corticostatins, compete with ACTH for binding on its receptor, thus resulting in decreased cortisol production and secretion
Other neuropeptides, signaling molecules, components of oxidative stress and the impaired adrenal blood flow contribute to adrenal insufficiency.
Some inflammatory factors may cause glucocorticoid resistance at the level of target cell, affecting vital steps of the glucocorticoid receptor signaling.
accessed 23 May 2012

13. Now that you are considering adrenal dysfunction..
What should I do?

14. Was adrenal dysfunction present before surgery?
Ask for symptoms
Weakness and fatigue
Anorexia, nausea, vomiting
Abdominal pain
Myalgia or arthralgia
History of steroid use?
Prednisone, Medrol, Decilone
Celestamine, Claricort
Nasal sprays (?)
History of pituitary dysfunction?
History of low TSH and FT4?
Brain surgery / trauma / irradiation / Sheehan’s?
Look for:
Decreased body hair
Vitiligo
Increased pigmentation
Cooper M, Stewart P. N Engl J Med ;8

15. Features suggesting corticosteroid insufficiency
Clinical problems
Hemodynamic instability
Ongoing inflammation with no obvious source
Multiple-organ dysfunction
Laboratory findings
Hyponatremia
Hyperkalemia
Hypoglycemia
Eosinophilia
Rarely seen in ICU patients
Cooper M, Stewart P. N Engl J Med ;8

16. Before you test for cortisol..
Septic shock and ARDS should be treated with glucocorticoids
Septic shock
SIRS
Infection
End-organ damage
Refractory hypotension
ARDS
Hypoxia
Chest X-Ray: Bilateral diffuse infiltrates of the lungs
No cardiovascular lesion
PaO2/FiO2 ratio less than 200
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

17. Cooper M, Stewart P. N Engl J Med 2003. 348;8

18. Cooper M, Stewart P. N Engl J Med 2003. 348;8

19. Corticotropin test / ACTH stimulation test
Baseline cortisol
Administer synthetic ACTH (synacthen) 250g IV over 2 minutes (do not use 1 g)
Get cortisol at 30 and 60 mins
Adequate response:  Cortisol ≥ 9g/dl
Where can I get ACTH (synacthen)?
Makati Medical Center (clinic of Dra. Crisostomo or Dra. Isidro): Php500
St. Luke’s Medical Center QC DTEC ( local 5210): Php4,350
The Medical City and UST: in-hospital use only

20. American College of Critical Care Medicine
At this time, adrenal insufficiency in critical illness is best diagnosed by:
 cortisol (after 250 µg cosyntropin) of <9 µg/dL
Random total cortisol of <10 µg/dL
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

21. ACTH is not available in my area, can’t I just do a random cortisol assay?
Yes but if your result is between µg/dL, still better to do corticotropin test.
My patient is hypotensive! Isn’t that stress enough to stimulated the adrenals?
It may sound plausible, but I can’t give you any evidence to recommend such at this time.

22. Can I do an insulin tolerance test instead of giving ACTH?
No, this is contraindicated in patients with ischemic heart disease.
My lab doesn’t do cortisol. Can I just go clinical and treat?
No evidence that treatment may be harmful, so maybe could be acceptable.

23. Corticosteroid-replacement doses
Cooper M, Stewart P. N Engl J Med ;8

24. Glucocorticoid supplementation
For severe surgical stress, including cardiothoracic surgery:
IV hydrocortisone 150mg/day (eg 50mg q8h)
Taper over next 2-3 days post-surgery
For myocardial infarction:
Same dose as above
Taper once clinical condition stabilizes
Septic shock / major trauma / life-threatening complication
Maximum 200mg/day IV hydrocortisone (eg 50mg q6h)
Jung C et al. Med J Aust :

25. Are glucocorticoids beneficial?
69% of patients with functional hypoadrenalism (Cortisol < 30 g/dL or  cortisol ≤ 9 g/dL) could be weaned from treatment with vasopressors within 24 h (p<0.031)
This benefit was not seen in patients with normal adrenal response
Mortality was also lower in the hydrocortisone-treated Adrenal Insufficiency patients: 21% vs 45% (p < 0.01)
Rivers EP, Gaspari M, Saad GA et al. Chest 2001; 119:

26. More data is needed re the benefits of treatment
The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation.
Please contribute to our knowledge through research
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6

27. Wow, this cardiologist really takes everything into consideration!
Let’s work this patient up for adrenal dysfunction and give steroids if warranted
Hey I should have thought of that earlier!

28. Adrenal Dysfunction following Cardiac Surgery
JM Co, MD, FPCP, FPSEM
Endocrinology, diabetes and metabolism
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